Phototherapeutical method and system for the treatment of inflammatory and hyperproliferative disorders of the nasal mucosa

ABSTRACT

A phototherapeutical apparatus is described, including a light source, generating high intensity visible light, in some embodiments in combination with ultraviolet light, an optical guidance system, and a patient interface. The patient interface can be insertable at least partially into a nasal cavity and is operable to apply the generated light to a tissue surface of the nasal cavity. Applying the apparatus includes providing the phototherapeutical apparatus, preparing for the application of the apparatus, inserting the patient interface into the nasal cavity, and applying the generated light by the patient interface to a tissue surface of the nasal cavity, wherein the tissue of the nasal cavity has an inflammatory or a hyperproliferative disease. The inflammatory diseases include rhinitis, sinusitis, and rhinosinusitis. A photodynamical therapy is also described, applying photosensitizing substances before the treatment with light. The phototherapeutical method is also effective for the prevention of inflammatory or hyperproliferative diseases.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.10/440,690, filed May 19, 2003, which is incorporated by referenceherein. The present Application is also a continuation-in-part of U.S.application Ser. No. 10/410,690, filed Apr. 9, 2003, which is acontinuation of International Application No. PCT/HU01/00102, filed Oct.24, 2001, which claims priority from Hungarian Application No. P0103279, filed Aug. 10, 2001, all of which are also incorporated byreference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to the treatment and prevention ofinflammatory and hyperproliferative diseases of body cavities, moreparticularly to the treatment and prevention of diseases of the nasalcavity by phototherapeutical methods.

2. Description of the Related Art

The treatment and prevention of inflammatory diseases of the nasalmucous membrane and paranasal sinuses is an unsolved problem. Thesediseases include allergic rhinitis, commonly referred to as hay fever,vasomotor rhinitis, non-allergic eosinophilic rhinitis, chronicsinusitis, which is the inflammation of the paranasal sinuses, and nasalpolyps.

Rhinitis is an inflammatory disorder of the nasal mucous membrane, whichis characterized by nasal itch, sneeze, nose running, nasal blockage,and rarely by loss of smelling. The inflammation of the nasal mucousmembrane is frequently associated with the inflammation of the paranasalsinuses (rhinosinusitis, chronic sinusitis). As a consequence of thefrequent and persistent inflammation of the mucous membranehyperproliferative lesions, or so-called polyps develop on the mucousmembrane.

One characteristic disease is the allergic rhinitis, commonly referredto as hay fever. The allergic rhinitis is the most frequent allergicdisease affecting 10-20% of the population. The number of patients withallergic rhinitis, especially in the well developed industrial countriesincreased very rapidly in the last few years. Because of the high numberof patients the direct and indirect costs of this disease are great.

Although hay fever is not a very severe disease, its unpleasant symptomsworsen the quality of life considerably. Hay fever is frequentlyassociated with allergic conjunctivitis and sometimes with generalsymptoms. The symptoms last only for a few months in some patients(seasonal rhinitis), while in others they last the whole year (perennialrhinitis).

The symptoms of the allergic diseases develop as follows. An allergenenters the body and induces the production of a specific IgE, whichbinds to specific receptors on the surface of mast cells. Aftersubsequent exposure the allergen crosslinks the IgE receptors, resultingin mediator release from the mast cells. These mediators are responsiblefor the development of the symptoms in patient.

As a result of this activation histamine and other preformed mediatorsare released from the mast cells. In the mast cells new inflammatorymediators are produced attracting further inflammatory cells into themucous membrane (Howarth P H, Salagean M, Dokic D: Allergic rhinitis:not purely a histamine-related disease. Allergy 55: 7-16, 2000).

At present there is no treatment for rhinitis, which would result in acomplete elimination of the symptoms. The increased number ofinflammatory cells in the nasal mucous membrane release mediators, whichare responsible for the clinical symptoms. Often antihistamines are usedlocally or systemically for the blocking of the released mediators.Sodium cromoglycate is available for the inhibition of the release ofmediators. Finally, corticosteroids are used locally or systemically forthe blocking of the synthesis of new mediators. In special cases adesensitizing therapy might be used. The pathogenesis of the developmentof the clinical symptoms is already well known. However, the presentlyavailable drugs often do not eliminate the symptoms. Therefore, everynew method for the treatment of this disease has a great medicalsignificance.

A further characteristic disease is vasomotor rhinitis. Vasomotorrhinitis is an inflammatory disorder of the nasal mucous membrane withunknown origin. The clinical symptoms are largely similar to that ofallergic rhinitis: permanent nasal blockage, nasal itch, sneeze, noserunning, and rarely loss of smelling. Mastocyte-activating mediatorscause the symptoms. These are released from the nerve endings of thenasal mucous membrane upon irritation.

A further characteristic disease is the nonallergic eosinophilicrhinitis. This disease is characterized by the high number ofeosinophils in the nasal secretions and by the lack of an allergicorigin. The disease is frequently associated with the development ofnasal polyps, the hyperproliferative condition of the nasal mucousmembrane. The clinical symptoms are the same as in allergic rhinitis.

Additional diseases are rhinosinusitis and sinusitis. The inflammationof the paranasal sinuses is frequently associated with the inflammatorycondition of the nasal mucous membrane (nasosinusitis). The isolatedinflammation of the paranasal sinuses is also a frequent disease(sinusitis). This disease has often an allergic origin, although itsexact cause remains unknown. There is no well-tested treatment, thususually the same therapy is used as for rhinitis.

Ultraviolet light has been used for more than twenty years for thetreatment of allergic and auto-immune skin diseases. In varioustreatments and procedures ultravioletB light (280 nm-320 nm) andultraviolet-A light (320 nm-400 nm) is used typically. The ultravioletlight inhibits the antigen-induced cellular immune response and is ableto induce tolerance (Streilein J W, Bergstresser P R: Genetic basis ofultraviolet-B on contact hypersensitivity. Immunogenetics 27: 252-258,1988).

The ultraviolet light suppresses the immune reaction by inhibiting theantigen presentation and by inducing T-cell apoptosis. Irradiation ofthe skin with ultraviolet-B light or ultraviolet-A light on an areapreviously photosensitized by psoralen is known to inhibit theimmunological processes in the skin. For the treatment of skin diseasesthere are a number of phototherapeutical devices available.

These phototherapeutical devices include ultraviolet light sources.These light sources might be classified based on, for example, theiroperational principle, output energy or power, mode of operation(impulse or continuous), and whether they are emitting monochromatic ormultiwavelength light.

In early treatments broad band ultraviolet B (BB-UVB) light sources wereused. In recent years more efficient narrow band ultraviolet B (NB-UVB)light sources became popular (Degitz K, Messer G, Plewig G, Röcken M:Schmalspektrum-UVB 311 nm versus Breitspektrum-UVB. Neue Entwicklungenin der Phototherapie. Hautarzt 49: 795-806, 1998).

Our previous investigations of psoriatic patients indicated that the 308nm xenon chloride excimer laser is more effective for phototherapeuticaltreatments than the NBUVB light sources (Bónis B, Kemény L, Dobozy A,Bor Zs, Szabó G, Ignácz F: 308 nm UVB excimer laser for psoriasis.Lancet 35: 1522, 1997; Kemény L, Bónis B, Dobozy A, Bor Z, Szabo G,Ignacz F: 308-nm excimer laser therapy for psoriasis. Arch Dermatol.137: 95-96, 2001).

Phototherapeutical treatments improved significantly with the appearanceof ultraviolet light delivering optical systems. Such an ultravioletlight delivering phototherapeutical system with fiber optic is used inthe Saalmann Cup instrument, in which the concentrated ultraviolet lightis coupled into a fiber optic cable. Therefore, it is suitable for thetreatment of smaller lesions of the skin or mucous membrane (Taube K M,Fiedler H: Hochkonzentrierte UV Bestrahlung kleiner Hautbezirke miteinem neuen Punktstrahler. Grundlagen und klinische Ergebnisse. DeutscheDermatologe, 10: 1453, 1992).

However, the Saalmann Cup can not be introduced into smaller bodycavities because of its large contact area and because of the thicknessof the used fiber optic cable. This device can be used in body cavitieswhere the distal end of the fiber optic cable and the area to be treatedcan be visually controlled, such as the oral cavity. For this reason,this device is unsuitable for the treatment of body areas, which cannotbe visually controlled, such as the nasal and paranasal mucous membrane,the gastrointestinal, and the urogenital mucous membrane.

Although ultraviolet light has been used for the treatment ofhyperproliferative and inflammatory skin diseases for many years, it hasnot been used for the treatment of common, immunologically mediateddisorders of the nasal mucous membrane. In the U.S. Patent Applicationby Lajos Kemény, Zsolt Bor, Gábor Szabó, Ferenc Ignácz, Béla Rácz, andAttila Dobozy, entitled: “Phototherapeutical Apparatus and Method forthe Treatment and Prevention of Diseases of Body Cavities”, filed Apr.9^(th) 2003, hereby incorporated by reference in its entirety, aphototherapeutical apparatus and method was described for the treatmentof inflammatory and hyperproliferative disorders of the nasal mucosa andparanasal sinuses, such as allergic and non-allergic rhinitis, vasomotorfhinitis, allergic rhinosinusitis, and nasal polips. This methodutilized ultraviolet light. Ultraviolet light was reported to beeffective for the treatment of different forms of rhinitis, includinghay fever. Also, ultraviolet light suppressed the development of nasalpolips.

Neuman and Finkelstein used narrow-band, low energy, red-lightphototherapy for the treatment of the nasal mucous membrane and theyfound it effective for perennial allergic rhinitis but not for nasalpolyposis (Neuman I., Finkelstein Y. Narrow-band red light phototherapyin perennial allergic rhinitis and nasal polyposis. Ann Allergy AsthmaImmunol 78: 399-406, 1997). Neumann and Finkelstein irradiated the nasalmucosa using a 660 nm light emitting diode (LED) with a dose of 3J/nostril day. They referred to their treatment as “a low-energystimulation” as they used a 4 mW light emitting diode. As the totalsurface of the mucosa of one nostril is approximately 15 cm², the nasalmucosa was illuminated with a total daily dose of approximately 0.2J/cm².

In our patients cohort, we were not able to demonstrate the efficacy ofthis low energy, low intensity red light phototherapy for the treatmentof hay fever. It should be noted, however, that high energy, highintensity visible light phototherapy has not previously been used forthe treatment of inflammatory and hyperproliferative disorders of thenasal mucosa and paranasal sinuses such as allergic and non-allergicrhinitis, vasomotor rhinitis, allergic rhinosinusitis, and nasal polips.

The photodynamic therapy (PDT) has been used for the last hundred yearsfor the treatment of cancers. Many studies confirmed the efficacy of PDTfor the treatment of different tumors in the last 30 years. In topicalPDT, 5-aminolevulinate (ALA) is applied into the area to be treated. ALAis converted in situ into the active endogenous photosensitizerprotoporphyrin IX, which sensitizes the hyperproliferative cells.Illumination of the lesions with high intensity visible light results inthe production of singlet oxygen molecules, the presence of whichcausing the subsequent death of the sensitized cells.

Recently a new, highly selective photosensitizer compound, methyl5-aminolevulinate has also been introduced for use in topical PDT andmany different studies confirmed its efficacy for the treatment ofpremalignant and malignant skin lesions (R. Szeimes et al.: Photodynamictherapy using topical methyl 5-aminolevulinate compared with cryotherapyfor actinic keratosis: a prospective randomized study. Journal of theAmerican Academy of Dermatology, vol. 47, p. 258, 2002) Although PDT hasbeen used in many applications, it has not been used for the treatmentof hay fever or nasal polips yet.

There are a number of ultraviolet light delivery systems, which uselasers. For example, the light of the 308 nm xenon chloride excimerlaser can be guided by fiber optic cable for the cleaning of root canalsby ablation (Folwaczny M, Mehl A, Haffaer C, Hickel R: Substance removalon teeth with and without calculus using 308 nm XeCl excimer laserradiation. An in vitro investigation. J. Clin. Periodontol 26: 306-12,1999). The 308 nm xenon chloride excimer laser is also suitable to treatartherosclerosis by treating the blood vessel walls (U.S. Pat. No.4,686,979), or to enhance the cardiac oxygenization with transmyocardiallaser revascularisation (U.S. Pat. No. 5,976,124), or inhibitingneovascularisation during angioplasty by destroying myocardial cells(U.S. Pat. No. 5,053,033).

These systems share the common feature that the high-energy ultravioletlight at the end of the light delivering system is focused on smallareas of only a few hundred microns in diameter. The photoablationproduced by the intense ultraviolet light removes the undesiredmaterial. However, the intense ultraviolet light damages the tissueswith its ablative effect.

It is also known that larger skin lesions can be treated by using anumber of small fiber optic cables (U.S. Pat. No. 6,071,302; WO9607451,Asawanonda P, Anderson R R, Chang Y, Taylor C R: 308-nm excimer laserfor the treatment of psoriasis: a doseresponse study. Arch Dermatol 136:619-24, 2000).

Phototherapeutical systems attached to endoscopes are also used for thephotodynamic treatment of tumors, such as bladder carcinoma or bronchialcancer. However, these instruments have special distal ends for tumortreatment (U.S. Pat. Nos. 4,313,431; 4,612,938; 4,676,231; 4,998,930;5,146,917).

At present, the phototherapeutical systems delivering light consist of ahand piece specifically shaped to a specific treatment. As such, theyare either unsuitable or inconvenient for the treatment of small bodycavities such as the nasal cavity with visual control.

SUMMARY OF THE INVENTION

Briefly and generally, embodiments of a phototherapeutical apparatus aredescribed, the apparatus including: a light source, operable to generatehigh intensity visible light, an optical guidance system, operable toreceive and guide the high intensity visible light of the light source,and a patient interface, operable to receive the guided light from theoptical guidance system, wherein the patient interface is operable toapply the guided light to a tissue surface of a nasal cavity. In someembodiments the patient interface is insertable at least partially intoa nasal cavity.

Further, embodiments of a method of treating diseases is described. Themethod includes providing a phototherapeutical apparatus, which includesa light source, operable to generate high intensity visible light, anoptical guidance system, coupled to the light source, and a patientinterface, coupled to the optical guidance system. The method furtherincludes preparing for the application of the phototherapeuticalapparatus, inserting at least partially the patient interface into anasal cavity, generating high intensity visible light with the lightsource, coupling the high intensity visible light into the patientinterface through the optical guidance system, and applying the highintensity visible light by the patient interface to a tissue surface ofthe nasal cavity, wherein the tissue of the nasal cavity has aninflammatory disease or a hyperproliferative disease.

Examples of inflammatory diseases include the inflammatory diseases ofthe nasal cavity. Research showed that single or repeated irradiation ofthe nasal mucous membrane and paranasal sinuses with high intensityvisible light, or with a combination of visible light with ultravioletlight (of the UVB or UVA type, or both) suppress the clinical symptomsof rhinitis, sinusitis, and rhinosinusitis, and result the regression ofnasal polyps.

In some embodiments of the phototherapeutical method photodynamictherapeutical methods are included, where a photosensitizing substance,such as deltaaminolevolunic acid is applied to the tissue surface beforeirradiation with light.

The phototherapeutical apparatus is also effective for the prevention ofinflammatory diseases or hyperproliferative diseases. In theseembodiments of the method phototherapy is applied before the appearanceof clinical symptoms of the disease.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the present invention and forfurther features and advantages, reference is now made to the followingdescription taken in conjunction with the accompanying drawings.

FIG. 1 illustrates an embodiment of the phototherapeutical apparatusaccording to the invention.

FIGS. 2A-B illustrate exemplary implementations of the light source andthe phototherapeutical apparatus according to an embodiment of theinvention.

FIG. 3 illustrates an exemplary implementation of the optical couplingunit according to an embodiment of the invention.

FIG. 4 illustrates an exemplary implementation of the patient interfaceaccording to an embodiment of the invention.

FIG. 5 illustrates an exemplary implementation of the patient interfaceaccording to an embodiment of the invention.

FIG. 6 illustrates an exemplary implementation of the patient interfaceaccording to an embodiment of the invention.

FIG. 7 illustrates an exemplary implementation of the patient interfaceaccording to an embodiment of the invention.

FIG. 8 illustrates an exemplary implementation of the patient interfaceaccording to an embodiment of the invention.

FIG. 9 illustrates a phototherapeutical apparatus including a flexibleendoscope, according to an embodiment of the invention.

FIG. 10 illustrates steps of the phototherapeutical method, according toan embodiment of the invention.

FIG. 11 illustrates the decrease of clinical symptoms due to treatmentwith an embodiment of the phototherapeutical method, according to anembodiment of the invention.

FIG. 12 illustrates the decrease of clinical symptoms due to treatmentwith an embodiment of the photodynamic therapeutical method, accordingto an embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Embodiments of the present invention and their advantages are bestunderstood by referring to FIGS. 1-12 of the drawings. Like numerals areused for like and corresponding parts of the various drawings.

The Phototherapeutical Apparatus

The phototherapeutical apparatus, according to embodiments of thepresent invention is suited for the treatment and prevention of commoninflammatory diseases of the body. In some applications thephototherapeutical apparatus is used for the treatment and prevention ofthe diseases of a nasal mucous membrane and paranasal sinuses such asallergic rhinitis (hay fever), vasomotor rhinitis, nonallergiceosinophilic rhinitis, chronic sinusitis (inflammation in the paranasalsinuses), or nasal polyps. Some embodiments of the phototherapeuticalapparatus utilize visible light. Some embodiments utilize a combinationof visible light and ultraviolet light. Some embodiments utilize highintensity light.

FIG. 1 illustrates a phototherapeutical apparatus 100, according to anembodiment of the invention. Phototherapeutical apparatus 100 includes alight source 1. Light source 1 is operable to generate a light beam 2 ofvisible light, ultraviolet light, or a combination of visible andultraviolet light. Light source 1 is operable to generate high intensitylight. Light beam 2 enters into an optical coupling unit 3, where lightbeam 2 is focused. The focused light beam is coupled by optical couplingunit 3 into an optical guidance system 4. Optical guidance system 4guides the focused light beam into a patient interface 5. Patientinterface 5 is insertable at least partially into a body cavity, whereit applies the light beam to a tissue surface of a body cavity. FIG. 1illustrates an embodiment, where the body cavity is the nasal cavity andthe patient interface is inserted through a nostril 6.

In some embodiments light source 1 generates a continuous light beam, inothers a slowly oscillating light beam. For example, in some embodimentsthe frequency of oscillations can be below about 100 Hertz. In variousembodiments the continuous light beam and slowly oscillating light beamwill be jointly referred to as quasi-continuous light beam.

Light source 1 can be, for example, a monochromatic light source or amultiwavelength light source.

A variety of monochromatic light sources, such as lasers, can be used aslight source 1. Examples include any type of diode lasers or otherlasers emitting high intensity light in the visible spectrum. Also, avariety of multiwavelength light sources can be used as light source 1.Examples include electric discharge lamps, arc lamps filled with xenon,mercury vapour, xenon and mercury vapour, fluorescent lamps, and lightemitting diodes (LEDs).

In some embodiments substantially all of the light, generated by lightsource 1, is visible light, i.e. it has a wavelength in the visiblespectrum, between about 400 nm and about 700 nm. In some embodiments thewavelength is in the high energy portion of the visible spectrum,between about 400 nm and about 600 nm.

In embodiments the generated visible light has a dose up to about 100J/cm² on the targeted tissue. In some embodiments light beams with adose between about 10 J/cm² and about 100 J/cm² will be referred to ashigh intensity light. The range of the dose of the light may depend onthe specific patient. For some patients a light with a dose of, forexample 4J/cm² or 7 J/cm² may be already high intensity.

In some embodiments light source 1 generates a certain amount ofultraviolet light simultaneously with the visible light. The ultravioletlight can have a wavelength in the ultraviolet-B (280 nm-320 nm) andultraviolet-A (320 nm-400 nm) part of the spectrum.

FIG. 2A illustrates an example of light source 1, operable to generatevisible light, ultraviolet light, or a combination of visible andultraviolet light, according to embodiments of the invention. Anelectric power supply unit 7 is connected to electrodes 11 by wires 8.Electrodes 11 enter the internal space of quartz bulb 12, which isfilled with gas. The electric power, provided by electric power supply 7causes an electric discharge in the gas. During this discharge light isgenerated. The wavelength of the light depends, among others, on thechemical composition of the gas. With a suitable choice of the chemicalcomposition of the gas the generated light will have a wavelength in thevisible spectrum or in the ultraviolet spectrum. In some embodiments thegas or gas mixture in quartz bulb 12 can include xenon, argon, andmercury vapor, and any other gas that emit light substantially in thevisible spectrum, possibly with a portion emitted in the ultravioletspectrum. Part of the light, generated in the discharge space,propagates directly towards focusing lens 15. Other portions of thegenerated light propagate in other directions. Part of these portionsare reflected by concave mirror 9 toward focusing lens 15. Focusing lens15 focuses all incoming light efficiently into a light beam 2. Thefocused light beam 2 leaves housing 10 through an output opening 14 andreaches an optical filter 13. In some embodiments optical filter 13transmits visible light, ultraviolet A, or ultraviolet B, or anycombination of light. From optical filter 13 the filtered and focusedlight beam 2 is coupled into an optical guidance system 4.

The volume of the discharge space in quartz bulb 12 varies in the rangeof about 1 mm³ to about 0.1 mm³. In some embodiments the discharge spaceis positioned approximately in the focus of concave mirror 9, so concavemirror 9 can efficiently focus the emitted light onto focusing lens 15.

FIG. 2B illustrates a phototherapeutical apparatus 100, according to arelated embodiment of the invention. Power supply 7 provides adjustablepower for apparatus 100. Power supply 7 may include a medical gradeisolation transformer. The isolation transformer also providesprotection from electrical shock. Quartz bulb 12 is operable to generatelight with a wavelength between about 280 nm and about 700 nm. In someembodiments quartz bulb 12 is operable to generate light with awavelength between about 280 nm and about 600 nm. An embodiment ofquartz bulb 12 is an electric microdischarge lamp. In embodiments thelength of discharge space, or “arc”, is between about 1 mm and about 10mm. Because of the smallness of the discharge volume it is easy tocollect the generated light and to couple it into optical guidancesystem 4. As an example, an electric micro-discharge lamp with a powerof about 35 watts may output between about 0.1 watts to about 2 watts atpatient interface 5.

Previous examples of arc lamps include mercury and mercury xenon lamps,described, for example, by Hartmann et al. in Patent Application WO02/13905. In these lamps the discharge space is bigger. Accordingly,these lamps need a power of 500 to 1500 watts to output 2 to 4 watts atpatient interface 5. In contrast, embodiments of the present inventionutilize micro-discharge lamps. These substantially smaller dischargelamps can operate with a power of about 35 watts. Micro-discharge lampsalso produce much less heat. Therefore, in some embodiments noventilation is necessary to cool the micro-discharge lamp during usage.Because of the small lamp size some embodiments of thephototherapeutical device are portable. For example, embodiments of thedevice can be powered through the cigar lighter of an automobile.

The generated light beam 2 is coupled by optical coupling unit 3 intooptical guidance system 4. Optical coupling unit 3 includes opticalfilter 13 and beam shutter 110. Optical filter 13 is operable to selecta range of wavelengths from the overall wavelength range of light beam2. Commercially available optical filters 13 include SCHOTT GG 400(manufactured by Schott A. G., Germany), which is operable to filter outthe ultraviolet portion of light beam 2 with wavelengths below about 400nm. Optical filter SCHOTT WG 320 (Schott A. G., Germany) is operable tofilter out the ultraviolet-B portion of the spectrum, below about 320nm. Beam shutter 10 is controlled and monitored by a control panel 106.Control panel 106 may include an electronic timing unit, which isoperable to log the operational ON time of power supply 7. The intensityof light beam 2 is adjustable by controlling the current output of powersupply 7. Phototherapeutical apparatus 100 can be pre-programmed throughcontrol panel 106. Pre-programming may include selecting a treatmentirradiant dosage by setting the timing unit and adjusting the intensityof light beam 2 by setting the current of power supply 7. Someembodiments may include a footswitch 104. Footswitch 104 can be used toconvenient application of apparatus 100. For example, footswitch can beused to start a pre-programmed application of apparatus 100.

Light beam 2 is coupled by optical coupling unit 3 into optical guidancesystem 4. Optical guidance system 4 might provide additional opticalfiltering. Embodiments of optical guidance system 4 include an opticalcable with a core diameter between about 1 mm and about 10 mm. Opticalguidance system 4 couples light beam 2 into patient interface 5. Patientinterface 5 may be inserted into the nasal cavity of a patient. FIG. 2Bshows a hollow plastic tip as a patient interface 5. Several additionalembodiments of patient interface 5 will be described below. Patientinterface 5 might also provide additional optical filtering. Patientinterface 5 may include a tip which transmits visible light but does nottransmit ultraviolet light, or a tip which transmits both visible andultraviolet light.

FIG. 3 illustrates an embodiment of optical coupling 3. Light beam 2entering optical coupling unit 3 is directed by a dichroic mirror 16into optical guidance system 4 through a lens system 17. Dichroic mirror16 simultaneously performs a spectral filtering of light beam 2.

In some embodiments optical guidance system 4 is also applicable toguide back reflected light, reflected from the site of application. Thelight emerging from the site of the application passes dichroic mirror16 and can be detected through an observing optical device 19 to assistthe application of the phototerapeutical device.

Optical guidance system 4 can be, for example, an optical cable or armsuitable to guide light. The optical cable or arm can be formed of anyone of a large number of known suitable materials, among others quartzglass or capillary tubes filled with a liquid capable of guiding light,wherein the internal surface of the capillary tubes are covered withultraviolet reflecting material. The diameter of the optical cable canbe between about 1 micron and about 10 mm. In some embodiments opticalguidance system 4 also performs a spectral filtering of light beam 2.

FIG. 4 illustrates an embodiment of patient interface 5, suitable forthe treatment of the nasal mucous membrane and paranasal sinuses.Patient interface 5 is suited to be positioned at least partially in thenostril or nasal cavity of a patient and guide light beam 2 onto thetissue surface to be treated. Many variations of patient interface 5 canbe constructed and are meant to be within the scope of the invention.

In the embodiment of FIG. 4 optical guidance system 4 is attached tohandgrip 20. The guided light enters from optical guidance system 4through handgrip 20 into optical tube 22 and propagates into a taperedend piece 24. A head 25 of patient interface 5 is coupled to opticaltube 22 by a fastener 23. A scanning light source 27 is included toilluminate the area of the tissue surface to be treated. Scanning lightsource 27 is built into handgrip 20 and can be powered by either aninternal or an external power supply unit. Mirror 28 reflects thescanning light of scanning light source 27 onto the tissue surface to betreated. Light beam 2 and the scanning light propagate through outputopening 26 onto the tissue surface to be treated. The end of patientinterface 5, where light beam 2 leaves patient interface 5 is sometimesreferred to as the distal end. In the present embodiment the distal endis where output opening 26 is positioned. A magnifying glass 21 mountedonto patient interface 5 provides visual control of the application ofthe light of phototherapeutical apparatus 100.

FIG. 5 shows another embodiment of patient interface 5, wherein thelight beam 2 enters from optical guidance system 4 through a lens 29 ofhandgrip 20. Light beam 2 is then reflected on dichroic mirror 16, whichis mounted inside optical tube 22, and leaves patient interface 5through output opening 26 of head 25. In this embodiment scanning lightsource 27 is mounted inside handgrip 20. The scanning light passesthrough dichroic mirror 16 and is reflected by concave holed mirror 30to illuminate the tissue surface to be treated.

In various embodiments external scanning light sources are applied toilluminate the tissue area to be treated.

FIG. 6 illustrates another embodiment of patient interface 5. In thisembodiment optical guidance system 4 is coupled into a pen-shapedhandgrip 31. Light beam 2 enters pen-shaped hand grip 31 and isreflected by flat surface treating head 32. Flat surface treating headcan include, among others, a quartz prism or a flat mirror. Flat surfacetreating head 32 is coupled to pen-shaped handle 31 with a fastener 23.

FIG. 7 illustrates another embodiment of patient interface 5, which issuitable for the circular treatment of a body cavity, for example, thenasal cavity. In this embodiment optical guidance system 4 guides lightbeam 2 into pen-shaped grip 31, where it is reflected by circularreflector 33 in a circular manner. Circular reflector 33 can be, forexample, a conical or a spherical reflecting surface. Circularapplicator head 34, housing circular reflector 33, is coupled topen-shaped handle 31 with fastener 23. Body cavities, such as the nasalcavity can be treated with this embodiment in a circular manner.

FIG. 8 illustrates another embodiment of patient interface 5, which issuited for a spot treatment of tissue surfaces, such as the nasal mucousmembrane. Optical guidance system 4 guides light beam 2 into pen-shapedhandle 31, where it is guided onto a spot on the tissue to be treated byspot applicator 36. Spot applicator 36 can be, for example, aplano-parallel disk or a lens 36 made of quartz or plastic transparentto light. Spot applicator 36 is housed by spot applicator head 35, whichis fastened onto pen-shaped handle 31 by a fastener 23.

FIG. 9 illustrates another embodiment of patient interface 5, which issuited for a spot treatment of tissue surfaces, such as the nasal mucousmembrane. Light beam 2 generated by light source 1 is focused andcoupled by optical coupling unit 3 into optical guidance system 4.Optical guidance system is integrated into flexible endoscope 37.Flexible endoscope 37 is capped with patient interface 5. Patientinterface 5 includes a spot applicator 36. Spot applicator 36 can be,for example, a plano-parallel disk or a lens 36 made of quartz orplastic transparent to light. In some embodiments spot applicator 36 canhave a sloped distal end.

In order to illuminate the tissue surface to be treated, a scanninglight is provided by scanning light source 27. The generated scanninglight is guided through lens 41 into scanning optical cable 42. Scanningoptical cable 42 can be also integrated into flexible endoscope 37. Thescanning light illuminates the tissue surface to be treated throughpatient interface 5.

Light reflected from the illuminated tissue surface is conducted backfrom the illuminated tissue surface via image processing optical cable38, which can be integrated into flexible endoscope 37 as well. Imageprocessing optical cable 38 is coupled into image processing unit 39 tofacilitate visual control of the application of the phototerapeuticalapparatus.

In some embodiments optical guidance system 4 can be rotated withinflexible endoscope 37 by positioning unit 40, so that the direction oflight beam 2 emitted through patient interface 5 can be modified. Inother embodiments flexible endoscope 37 itself can be rotated bypositioning unit 40. These embodiments are useful for the treatment ofvarious body cavities, for example, a larynx, a digestive canal, andurogenital organs.

Some embodiments for the circular and the spot treatment of tissuesurfaces may include a Panoramic Annular Lens (PAL) optical system. APAL system, transparent to the light can be included into circularapplicator head 34 and spot applicator head 35. Including a PAL opticalsystem can be helpful for simultaneous treatment of tissue surfaces andoptical image processing.

Phototherapeutical Method

According to embodiments of the invention, a phototherapeutical method200 is described for the treatment and prevention of inflammatory andhyperproliferative diseases of body cavities, more particularly for thetreatment and prevention of common inflammatory diseases of the nasalmucous membrane and paranasal sinuses, including allergic rhinitis (hayfever), vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronicsinusitis (inflammation in the paranasal sinuses), and for the treatmentand prevention of hyperproliferative diseases, including nasal polyps (afrequent benign hyperproliferative lesion in chronic inflammatoryconditions of the nasal mucous membrane).

Phototherapeutical method 200 is based on the inventor's researchresults, which showed that the application of visible light, or acombination of visible and ultraviolet light to tissue surfaces in thenasal cavity decreases the number and the activity of inflammatory cells(mast cells, eosinophils, and lymphocytes) responsible for the mediatorrelease and synthesis in the mucous membrane, and thereby it reduces theclinical symptoms of inflammatory, hyperproliferative, and allergicdiseases.

FIG. 10 illustrates steps of phototherapeutical method 200. In step 204phototherapeutical apparatus 100 is provided, wherein phototherapeuticalapparatus 100 includes: light source 1, optical guidance system 4,coupled to light source 1, and patient interface 5, coupled to opticalguidance system 4. Phototherapeutical method 200 can be practiced withany embodiment of phototherapeutical apparatus 100, described earlier.

In some embodiments, light source 1 is operable to generate highintensity visible light. High intensity light includes light with a dosebetween about 10 J/cm² and about 100 J/cm². In some embodiments lightsource 1 generates visible light in the high energy portion of thespectrum, with wavelength between about 400 nm and about 600 nm. Whenvisible light is used alone, without combination with UV light, highintensity light achieves significant immunosuppression in the nasalmucosa. The present method of using high intensity visible light differsfrom other methods using low-intensity light emitting diodes. Some lowintensity methods apply red light in a dose of about 0.2 J/cm²,therefore the present method applies light in orders of magnitude higherdoses.

In step 204 some embodiments of photoherapeutical apparatus 100 includeessentially monochromatic light sources, other embodiments includemultiwavelength light sources. Embodiments with monochromatic lightsources include, for example, any type of diode lasers, or any otherlasers, which emit light in the visible spectrum.

Multiple wavelengths embodiments include, for example, discharge lampsand arc lamps. Each of these lamps can be filled, for example, withxenon, mercury vapour, and a mixture of xenon and mercury vapour. Otherembodiments include fluorescent lamps, light emitting diodes (LEDs), anddye lasers.

In step 206 a preparation for the treatment by phototheraputical method200 is performed. The preparation can include—in case of a combinedvisible and ultraviolet light treatment—determining a light threshold ofthe particular patient on a part of the patient's skin, which was notrecently exposed to sunlight. One measure of a light threshold is theMinimal Erythema Dose (MED). The MED is the smallest dose of combinedlight, which causes erythema on the patient's previously unexposed skinafter 24 hours. The MED is then used to determine the value of the firstdose, applied to the area to be treated. The preparation can furtherinclude treatment of the nasal mucosa with nasal decongestants todecrease the odema of the nasal mucosa in order to be able to illuminatelarger mucosa surfaces.

The preparation can further include selecting a suitable patientinterface 5 for practicing phototherapeutical method 200. This choicedepends, for example, on the location of the area of the tissue surfaceto be treated and the anatomy of the body cavity of the patient.

In step 212 high intensity visible light beam 2 is generated by lightsource 1.

In step 216 the generated high intensity visible light beam 2 is coupledinto patient interface 5 through optical guidance system 4.

In step 220 the generated high intensity visible light is applied bypatient interface 5 to a tissue surface of a nasal cavity. In someembodiments of the method, step 220 includes inserting patient interface5 at least partially into the nasal cavity. Patient interface 5 isinserted at the distal end.

In some embodiments of step 220, where the tissue surface is the nasalmucous membrane, a high intensity visible light was applied throughpatient interface 5 with a dose between about 10 J/cm² and about 100J/cm².

The treatment with such high intensity visible light can be repeated oneor more times per week. The repeated application of such high intensityvisible light can be performed with the same dose or with increasingdoses, depending on the patient's tolerance and on the improvements ofthe clinical symptoms.

In some embodiments of step 220, where the tissue surface is the nasalmucous membrane, the high intensity visible light was applied in a dosebetween about 10 J/cm² and about 100 J/cm², in combination withultraviolet-A light (320 nm-400 nm) in a dose between about 1 J/cm² andabout 10 J/cm², or ultraviolet-B light (295-320 nm) in a dose betweenabout 0.01 J/cm² and about 1.0 J/cm², or both. In some embodiments thehigh intensity visible light was the high energy portion of the visiblespectrum, with wavelength between about 400 nm and about 600 nm.

Research indicated that the clinical symptoms of the treated nasalmucous membrane improved considerably with the treatment. These symptomsinclude nasal blockage, nasal itch, nose running, sneezing, and itchingof the palate in patients with allergic rhinitis.

In several cases the symptoms improved when high energy visible lightwas applied, or visible light in combination with ultraviolet light.

In some embodiments of the method, the previously determined MED valueis used to determine the first dose, applied to the tissue surface to betreated.

FIG. 11 illustrates the improvement of hay fever symptoms of the nasalmucous membrane as a result of being treated by phototherapeutic method200. The illustrated embodiment of method 200 used visible light (400nm-700 nm) in high doses. The severity scores of hay fever (0=nosymptoms, 3=very severe symptoms) are shown before the treatment andafter a 3-week treatment. The treatment included using the same dosefour times per week. As shown, the clinical symptoms and complaints ofthe patients decreased significantly after the treatment.

Similar improvements were observed in the clinical symptoms of vasomotorrhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis, and inthe sizes of nasal polyps after treatment with phototherapeutical method200. The clinical symptoms decreased considerably after the treatment.

In some embodiments the preparation of step 206 includes increasing theefficacy of phototherapeutical method 200 by administeringphotosensitizing substances before the phototherapy with visible light.Sometimes this method is referred to as photodynamic therapy (PDT).Example for photosensitizing substances include porphirin precursorssuch as 5-aminolevulinate, or metabolites of porphirin precursors, orother synthetic porphirin precursors such as methyl 5-aminolevulinate.These materials can be used in concentrations between about 1% and about20%.

In some embodiments the preparation of step 206 includes increasing theefficacy of phototherapeutical method 200 by administering a combinedhigh intensity visible light with ultraviolet light. When a visiblelight is applied in combination with ultraviolet light, the minimalerythema dosis (MED) can be measured on a part of the patient's skin,which was not exposed to sunlight before starting the therapy. The MEDis the smallest ultraviolet dose, which induces erythema on a previouslyunexposed skin after 24 hours.

In step 220 the high intensity visible light in combination withultraviolet light is applied to the nasal mucous membrane. Theapplication can be started with a dose about 1.0×MED to about 2.0×MED,depending on the severity of the symptoms of the patient. Duringrepeated applications in some embodiments the dose remains approximatelyconstant. In other embodiments the dose is increased depending on thepatient's tolerance. Step 220 can be repeated once or several times perweek. Research showed that phototherapy inhibits rapidly and effectivelythe clinical symptoms of hay fever, including nasal blockage, nasalitch, nose running, sneezing and itching of the palate.

FIG. 12 illustrates the improvement of hay fever symptoms of the nasalmucous membrane as a result of being treated by the combinedvisible/ultraviolet phototherapeutic method 200. In this embodiment ofthe method light source 1 is an electric discharge lamp, emitting morethan 98% of its power with wavelength between about 320 nm and about 650nm and approximately 2% of its power with wavelength between about 295nm and 320 nm. The severity scores of hay fever (0=no symptoms, 3=verysevere symptoms) are shown before the treatment and after a 3-weektreatment. The treatment was applied twice per week with essentiallyconstant doses. All the clinical symptoms and complaints of the patientsdecreased substantially after the phototherapy.

Similar improvements are observed in the clinical symptoms of vasomotorrhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis, and thesizes of nasal polyps considerably decreased after such a combined highintensity visible light/ultraviolet phototherapy.

Phototherapeutical method 200 is also suitable for the prevention ofinflammatory and hyperproliferative diseases of nasal cavities. Forexample, in the case of seasonal allergic rhinitis phototherapeuticalmethod 200 can be started before the appearance of the clinicalsymptoms.

Similarly, phototherapeutical method 200 with photochemotherapy is alsosuitable for the prevention of the clinical symptoms of patients withseasonal allergic rhinitis. The treatment can be started before theappearance of the symptoms. The treatment can be administered once orseveral times per week depending on the tolerance of the patient.

Finally it is noted that the application of phototherapeutical method200 is significantly cheaper than presently practiced drug basedtreatments.

Potential Side Effects

When visible light is used in combination with ultraviolet light for thetreatment, the ultraviolet light might facilitate the appearance ofviral and bacterial infections on the treated areas because of itsimmunosuppressive effect. This effect is similar to the effect oftopical corticosteroides. However, the likelihood for these infectionsis lower than that of the presently used local immuno-suppressivepreparations, because light also has a direct microbicidal effect(Folwaczny M, Liesenhoff T, Lehn N, Horch H H: Bactericidal action of308 nm excimer-laser radiation: an in vitro investigation. JEndodontics, 24: 781-785, 1998). Furthermore, light also increases thedirect microbicidal activity of epithelial cells (Csató M, KenderessySzA, Dobozy A: Enhancement of Candida albicans killing activity ofseparated human epidermal cells by ultraviolet radiation. Br J Dermatol116: 469-475, 1987).

Practicing phototherapeutical method 200 with phototherapeuticalapparatus 100 is further illustrated through the following examples.

EXAMPLE 1

Treatment of Hay Fever with High Intensity Visible Light

The severe symptoms of a patient with ragweed-induced hay fever did notrespond to the antihistamine and topical corticosteroid therapy. Atexamination the patient complained of severe nasal blockage, nasalitching, nose running, frequent snecezing and itching of the nasalpalate. Phototherapy of the nasal mucous membrane was started. For thispurpose high intensity visible light of light source 1 was generated byan electric discharge lamp and the generated light beam 2 was coupled byoptical focusing using concave mirror 9 into optical guidance system 4.Optical guidance system 4 was an optical cable with a diameter of 5.0mm. The optical cable was connected to patient interface 5 shown in FIG.2B. The treatment of the nasal mucous membrane of the patient wasstarted with a dose of 50 J/cm². The complete time of a treatment was 15minutes and the treatment did not cause any complaint by the patient.The treatment was then repeated three times per week using the samephototherapeutical apparatus, but the irradiation dose was increased by20% each occasion. After the fourth treatment the symptoms andcomplaints of the patient decreased to a large extent and in the thirdweek after the nine treatment the patient was completely free ofsymptoms. The treatment was stopped and no recurrence was observed. Thepatient found this type of therapy to be more efficacious as compared tothe previously used therapies.

EXAMPLE 2

Treatment of Hay Fever with a Combination of High Intensity VisibleLight and Ultraviolet Light

A patient with severe hay fever due to ragweed allergy did not impoveunder conventional therapy with antihistamines and corticosteroids.Therefore, an embodiment of phototherapeutical method 200 wasadministered. A special light source 1 was used to generate ultravioletand high intensity visible light. The intensity of the light at theoutput end of patient interface 5 was 700 mW/cm². The UVB (300-320 nmwavelengths) content of light beam 2 was 1%, the UVA (320 nm-400 nm)content was 13%, and the remaining 84% was in the visible (400-650 nm)portion of the spectrum. The minimal erythema dosage (MED) was firstdetermined on the forearm of the patient not exposed to sunlightearlier, then a phototherapeutical treatment of the nasal mucousmembrane was started with a dose of 1×MED. The patient interface 5 shownin FIG. 2B was brought into contact with the mucous membrane and thissurface was irradiated during the treatment. The treatment wascontrolled visually under protection of ultraviolet protectingeyeglasses. This phototherapy was repeated three times per week. Afterthe sixth treatment the symptoms of the patient decreased considerably,and after the eighth treatment the patient became free of symptoms. Onemonth after stopping the therapy the patient was still free of symptoms.

EXAMPLE 3

Treatment of Hay Fever with Photodynamic Therapy

The clinical symptoms of a patient suffering from ragweed-induced hayfever did not respond satisfactorily after using antihistamines andtopical corticosteroid nasal drops. At examination the symptoms (nasalblockage, nasal itching, nose running, frequent sneezing, and itching ofthe nasal palate) of the patient were severe, therefore an embodiment ofa photodynamic therapy was performed. The nasal mucosa was treated with20% 5-deltaminolevalunic acid (DALA) lotion 3 hours before phototherapy.For the phototherapy, light source 1 of the type shown in FIG. 2B wasused, generating light with wavelengths between 300 nm and 700 nm. Theultraviolet part of the generated light was filtered out by choosing anon-ultraviolet-transmissive optical guidance system 4. The treatment ofthe nasal mucous membrane was started with a dose of 20 J/cm² usingpatient interface 5 shown in FIG. 2B. Photodynamic therapy was thenrepeated twice weekly. Patient interface 5 was brought into contact withthe nasal nucous membrane altogether in eight positions in each nostril.The treatment of the nostrils took approximately 10 minutes. Thesymptoms of the patient improved considerably after the second treatmentand after two weeks the patient was completely free of symptoms. Afterstopping the therapy the symptoms of the patient did not return.

EXAMPLE 4

Treatment of Nasal Polips with Photodynamic Therapy

A patient had a large polyp in the right nostril, that has been operatedalready several times. The patient had also severe perennialrhinosinusitis, possibly inducing the recurrence. A 20% DALA solutionwas applied to the nasal polip. Three hours thereafter visible lightphototherapy using light source 1 was used to generate and deliver highintensity visible light to the affected area. Light source 1 of the typeshown in FIG. 2B was used, generating light with wavelengths between 300and 700 nm. The ultraviolet part of the emitted spectrum was filteredout by choosing a non-UV-transmissive optical guidance system 4. Thetreatment of the nasal mucous membrane was started with a dose of 60J/cm² using patient interface 5 shown in FIG. 2B. Five days after onesingle treatment the nasal polyp disappeared without any scar formation.The photodynamic therapy was then repeated once weekly for 8 weeks.After stopping the therapy the nasal polip did not return. Allcomplaints of the patient disappeared as well.

Although the present invention and its advantages have been described indetail, it should be understood that various changes, substitutions, andalterations can be made therein without departing from the spirit andscope of the invention as defined by the appended claims. That is, thediscussion included in this application is intended to serve as a basicdescription. It should be understood that the specific discussion maynot explicitly describe all embodiments possible; many alternatives areimplicit. It also may not fully explain the generic nature of theinvention and may not explicitly show how each feature or element canactually be representative of a broader function or of a great varietyof alternative or equivalent elements. Again, these are implicitlyincluded in this disclosure. Where the invention is described indevice-oriented terminology, each element of the device implicitlyperforms a function. Neither the description nor the terminology isintended to limit the scope of the claims.

1. A method of treating tissue, comprising: selecting an illuminationdosage of visible light, wherein said illumination dosage is selected totreat a medical condition of a patient; and administering theillumination dosage of visible light to respiratory tissue of thepatient.
 2. The method of claim 1, wherein the illumination dosage is 4J/cm².
 3. The method of claim 1, wherein the illumination dosage is 7J/cm².
 4. The method of claim 1, wherein the illumination dosage isabout 100 J/cm².
 5. The method of claim 1, wherein the illuminationdosage is in a range between about 10 J/cm² and about 100 J/cm².
 6. Themethod of claim 1, wherein the respiratory tissue comprises nasal cavitytissue.
 7. The method of claim 1, wherein the respiratory tissuecomprises nasal mucosa.
 8. The method of claim 1, wherein therespiratory tissue comprises sinus tissue.
 9. The method of claim 1,further comprising administering a photosensitizer to the patient. 10.The method of claim 9, wherein the administering a photosensitizer tothe patient is performed prior to administering the illumination dosage.11. The method of claim 9, wherein the photosensitizer comprises aporphyrin precursor.
 12. The method of claim 9, wherein thephotosensitizer comprises 5-aminolevulinate.
 13. The method of claim 9,wherein the photosensitizer comprises a metabolite of a porphyrinprecursors.
 14. The method of claim 9, wherein the photosensitizercomprises a synthetic porphyrin precursor.
 15. The method of claim 9,wherein the photosensitizer comprises methyl 5-aminolevulinate.
 16. Themethod of claim 9, wherein the photosensitizer comprises a concentrationin a range between about 1% and about 20%.
 17. The method of claim 9,wherein the administering a photosensitizer comprises applying asystemic photosensitizer.
 18. The method of claim 9, wherein theadministering a photosensitizer comprises applying a topicalphotosensitizer.
 19. The method of claim 9, further comprisingadministering ultraviolet light to the respiratory tissue.
 20. Themethod of claim 9, wherein the medical condition comprises a polyp. 21.The method of claim 9, wherein the medical condition comprises asthma.22. The method of claim 9, wherein the medical condition comprisessinusitis.
 23. The method of claim 1, further comprising administeringultraviolet light to the respiratory tissue.
 24. The method of claim 23,wherein said administering ultraviolet light to the respiratory tissueis performed while administering said illumination dosage of visiblelight.
 25. The method of claim 23, wherein said ultraviolet light has awavelength in a range between about 280 nm and about 320 nm.
 26. Themethod of claim 23, wherein said ultraviolet light has a wavelength in arange between about 320 nm and about 400 nm.
 27. The method of claim 23,wherein the medical condition comprises a polyp.
 28. The method of claim23, wherein the medical condition comprises asthma.
 29. The method ofclaim 23, wherein the medical condition comprises sinusitis.
 30. Themethod of claim 1, wherein the visible light has a wavelength in a rangeof about 400 nm to about 700 nm.
 31. The method of claim 1, wherein thevisible light has a wavelength in a range of about 400 nm to about 600nm.
 32. The method of claim 1, wherein the medical condition comprises apolyp.
 33. The method of claim 1, wherein the medical conditioncomprises allergic rhinitis.
 34. The method of claim 1, wherein themedical condition comprises asthma.
 35. The method of claim 1, whereinthe medical condition comprises sinusitis.
 36. The method of claim 1,wherein the medical condition comprises an inflammatory disease.
 37. Themethod of claim 1, wherein said administering the visible lightcomprises directing the visible light towards a sinus.
 38. A method oftreating tissue, comprising: administering a photosensitizer to mucosaltissue in the nasal cavity of a patient; and delivering ultravioletlight to the nasal cavity so that the ultraviolet light is at leastpartially absorbed by the mucosal tissue to treat a medical condition.39. A method of treating tissue, comprising: selecting an illuminationdosage of phototherapeutical light; providing the phototherapeuticallight to a patient's tissue; receiving reflected light reflected fromthe patient's tissue; and generating an image based at least in partupon the reflected light.
 40. A phototherapeutical device, comprising: alight source adapted to provide an illumination dose of visible light; apatient interface, coupled to said light source, adapted to be insertedinto a nasal cavity of a patient and to administer the illumination doseof visible light to tissue within the nasal cavity; an image processingelement adapted to receive reflected light that is reflected from thetissue within the nasal cavity; and an image processor coupled to theimage processing element that generates an image of the tissue.
 41. Thephototherapeutical device of claim 40, wherein the image processingelement comprises an image processing cable.
 42. A phototherapeuticaldevice, comprising: a light source adapted to provide an illuminationdose of light of 700 mW/cm²; and a patient interface, adapted to beinserted into a patient's nasal cavity and adapted to deliver theillumination dose to the nasal cavity.
 43. The phototherapeutical deviceof claim 42, wherein the light source comprises a UVA light source. 44.The phototherapeutical device of claim 42, wherein the light sourcecomprises a UVB light source.
 45. The phototherapeutical device of claim42, wherein the light source comprises a visible light source.
 46. Thephototherapeutical device of claim 42, wherein the illumination dosecomprises 13% UVA light.
 47. The phototherapeutical device of claim 42,wherein the illumination dose comprises 1% UVB light.
 48. Thephototherapeutical device of claim 42, wherein the illumination dosecomprises 84% visible light.
 49. A phototherapeutical device,comprising: a light source adapted to provide an illumination dose oflight in a range between about 0.1 W and about 2 W; and a patientinterface, adapted to be inserted into a patient's nasal cavity andadapted to deliver the illumination dose to the nasal cavity.
 50. Aphototherapeutical device, comprising: a light source adapted to providean illumination dose of light in a range between 2 W and 4 W; and apatient interface, adapted to be inserted into a patient's nasal cavityand adapted to deliver the illumination dose to the nasal cavity.
 51. Aphototherapeutical device, comprising: a light source adapted to providean illumination dose of light of 20 J/cm² over approximately 10 minutes;and a patient interface, adapted to be inserted into a patient's nasalcavity and adapted to deliver the illumination dose to the nasal cavity.52. A phototherapeutical device, comprising: a light source adapted toprovide an illumination dose of light of 50 J/cm² over 15 minutes; and apatient interface, adapted to be inserted into a patient's nasal cavityand adapted to deliver the illumination dose to the nasal cavity.